Imperfect DNA mirror repeats in the gaggene of HIV-1 (HXB2) identify key functional domains and coincide with protein structural elements in each of the mature proteins

Lang

Description

A DNA mirror repeat is a sequence segment delimited on the basis of its containing a center of symmetry on a single strand, e.g. 5'-GCATGGTACG-3'. It is most frequently described in association with a functionally significant site in a genomic sequence, and its occurrence is regarded as noteworthy, if not unusual. However, imperfect mirror repeats (IMRs) having ≥ 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with protein structural elements – helices, β sheets and turns. In this study, the distribution of IMRs is evaluated in a polyprotein – to determine whether IMRs may be related to the position or order of protein cleavage or other hierarchal aspects of protein function. The gag gene of HIV-1 [GenBank: K03455 ] was selected for the study because its protein motifs and structural components are well documented. Results There is a highly specific relationship between IMRs and structural and functional aspects of the Gag polyprotein. The five longest IMRs in the polyprotein translate a key functional segment in each of the five cleavage products. Throughout the protein, IMRs coincide with functionally significant segments of the protein. A detailed annotation of the protein, which combines structural, functional and IMR data illustrates these associations. There is a significant statistical correlation between the ends of IMRs and the ends of PSEs in each of the mature proteins. Weakly symmetric IMRs (≥ 33%) are related to cleavage positions and processes. Conclusion The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DNA and that different levels of symmetry are associated with different functional aspects of the gene and its protein. The interaction between IMRs and protein structure and function is precise and interwoven over the entire length of the polyprotein. The distribution of IMRs and their relationship to structural and functional motifs in the protein that they translate, suggest that DNA-driven processes, including the selection of mirror repeats, may be a constraining factor in molecular evolution.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2007
• Nombre de lectures: 4
• Langue: English

Extrait

Pga e 1fo1  ( 3 apegum nr bet nor foaticnoitrup esops)

Published: 26 October 2007 Received: 28 September 2007 Virology Journal 2007, 4 :113 doi:10.1186/1743-422X-4-113  Accepted: 26 October 2007 This article is available from: h ttp://www.virologyj.com/content/4/1/113 © 2007 Lang; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited.

Abstract Background: A DNA mirror repeat is a sequence segmen t delimited on the basis of its containing a center of symmetry on a single strand, e.g. 5' -GCATGGTACG-3'. It is most frequently described in association with a functionally significant site in a genomic sequence, and its occurrence is regarded as noteworthy, if not unusual. Howe ver, imperfect mirror repeats (IMRs) having ≥ 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with pr otein structural elements – helices, β sheets and turns. In this study, the distribution of IMRs is evaluated in a polyprotein – to determine whether IMRs may be related to the position or order of protein cleavage or other hi erarchal aspects of protein function. The gag gene of HIV-1 [GenBank:K03455 ] was selected for the study be cause its protein motifs and structural components are well documented. Results: There is a highly specific relationship betw een IMRs and structural and functional aspects of the Gag polyprotein. The five longest IMRs in the polyprotein translate a key functional segment in each of the five cleavage pr oducts. Throughout the protein, IMRs coincide with functionally significant segments of the protei n. A detailed annotation of the protein, which combines structural, functional and IMR data illustrate s these associations. There is a significant statistical correlation between the ends of IMRs and the ends of PSEs in each of the mature proteins. Weakly symmetric IMRs ( ≥ 33%) are related to cleava ge positions and processes. Conclusion: The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DN A and that different levels of symmetry are associated with different functi onal aspects of the gene and it s protein. The interaction between IMRs and protein structure and function is precis e and interwoven over the entire length of the polyprotein. The distribution of IM Rs and their relationship to st ructural and functional motifs in the protein that they translate, suggest that DNA-driven processes, in cluding the selection of mirror repeats, may be a constraini ng factor in molecular evolution.

Virology Journal

Bio Med Central

Address: School of Contemporary Sciences, University of Abertay-Dundee, Bell Street, Dundee DD1 1HG, Scotland, UK Email: Dorothy M Lang - [e-mail]

Research Open Access Imperfect DNA mirror repeats in the gag gene of HIV-1 (HXB2) identify key functional domains an d coincide with protein structural elements in each of the mature proteins Dorothy M Lang

Background strand and identical terminal nucleotides. For example, in A DNA mirror repeat is a sequence segment delimited on the sequence below, TACACG is the mirror image of GCA- the basis of its containing a center of symmetry on a single CAT.